Depolarizing response of rat parathyroid cells to divalent cations.

López‐Barneo, José; Armstrong, Clay M.

doi:10.1085/jgp.82.2.269

Cited by 88 publications

(27 citation statements)

References 40 publications

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“…If hypercalcaemia persists, it increases PTH gene expression and parathyroid cell proliferation (reviewed by [16]). Since these effects could not be accounted for by simple differences in ionic permeabilities across the plasma membrane, studies carried out in the early 1980s led to the hypothesis that the effects of Ca 2+ o on parathyroid function could be ascribed to a divalent cation receptor, expressed at the external side of parathyroid cells [76]. Ten years later, the molecular identification of the CaR provided the link between PTH secretion and changes in plasma Ca 2+ o .…”

Section: Car Within the Ca 2+ O Homeostatic Systemmentioning

confidence: 99%

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Riccardi

Finney

Wilkinson

et al. 2009

Pflugers Arch - Eur J Physiol

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The capacity to sense and adapt to changes in environmental cues is of paramount importance for every living organism. From yeast to man, cells must be able to match cellular activities to growth environment and nutrient availability. Key to this process is the development of membrane-bound systems that can detect modifications in the extracellular environment and to translate these into biological responses. Evidence gathered over the last 15 years has demonstrated that many of these cell surface "sensors" belong to the G protein-coupled receptor superfamily. Crucial to our understanding of nutrient sensing in mammalian species has been the identification of the extracellular Ca(2+)/cation-sensing receptor, CaR. CaR was the first ion-sensing molecule identified in man and genetic studies in humans have revealed the importance of the CaR in mineral ion metabolism. Latter, it has become apparent that the CaR also plays an important role outside the Ca(2+) homeostatic system, as an integrator of multiple environmental signals for the regulation of many vital cellular processes, from cell-to-cell communication to secretion and cell survival/cell death. Recently, novel aspects of receptor function reveal an unexpected role for the CaR in the regulation of growth and development in utero.

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Section: Car Within the Ca 2+ O Homeostatic Systemmentioning

confidence: 99%

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Riccardi

Finney

Wilkinson

et al. 2009

Pflugers Arch - Eur J Physiol

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“…The dose-response relationship for the membrane potential of rat parathyroid cells as a function of extracellular calcium concentration (16) is shown in Fig. 2.…”

Section: B Electrical Properties Of Parathyroid Cellsmentioning

confidence: 99%

“…The intracellular calcium concentration at the peak hyperpolarization cannot be estimated very accurately from available data on rat parathyroid cells, but a rough estimate made by comparing intracellular and extracellular calcium concentrations measured in bovine parathyroid cells (17) indicates that the peak hyperpolarization occurs at an intracellular calcium concentration of approximately 300 nM. In the range where increasing calcium concentrations cause a large membrane depolarization, the same calcium concentrations also cause a large increase in the electrical resistance of the membrane (16). In principle, this combination of effects could be explained by the closing of potassium channels, since open potassium channels tend to hyperpolarize cells and since the closing of any channel tends to increase membrane resistance.…”

Section: B Electrical Properties Of Parathyroid Cellsmentioning

confidence: 99%

Regulation of Parathyroid Hormone Secretion*

1991

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Calcium is the most important physiological regulator of PTH secretion. Peak PTH secretion occurs at an intracellular calcium concentration of about 200 nM, regardless of the extracellular calcium concentration. We suggest, therefore, that intracellular calcium concentration is a regulator of PTH secretion that maintains calcium homeostasis. Other factors may be responsible for modulation of the intracellular calcium concentration, ultimately modulating PTH secretion. The "paradoxical" nature of the dependence of PTH secretion on the calcium concentration may be explained by considering PTH secretion to be unusual in a quantitative, rather than a qualitative, fashion. A possible mechanism for the control of PTH secretion by intracellular calcium, which involves calcium-activated potassium channels, is proposed. The parathyroid cell plasma membrane contains several sensors or channels by means of which the cell senses extracellular calcium. It is not clear whether these entities are coupled to each other or whether they function independently. Guanine nucleotide regulatory proteins are transducers of extracellular signals, including calcium. Several other second messengers that influence PTH secretion have also been described, but possible interactions between these messengers have not yet been determined.

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“…The mechanism (s) by which the parathyroid cell recognizes changes in the extracellular Ca concentration and transduces this information into the appropriate message(s) to modulate PTH release is not known. Recent electrophysiological data suggest the presence of an extracellular Ca receptor, which may control membrane potential and, perhaps, PTH release (2)(3)(4). In an attempt to develop probes to identify and characterize this and other cell surface constituents important in regulating PTH secretion, we have screened a library of monoclonal antibodies (MAbs) which bind to the cell surface of other neuroendocrine cells for reactivity with human parathyroid cells.…”

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Binding of Monoclonal Antibody (4F2) to its Cell Surface Antigen on Dispersed Adenomatous Parathyroid Cells Raises Cytosolic Calcium and Inhibits Parathyroid Hormone Secretion*

Posillico

Srikanta

Eisenbarth

et al. 1987

The Journal of Clinical Endocrinology & Metabolism

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In the course of characterizing monoclonal antibodies (MAbs) recognizing cell surface antigens on dispersed human parathyroid cells (dPTCs), we identified one MAb (4F2) that bound avidly to parathyroid cells and had marked effects on parathyroid function. The binding of MAb 4F2 to human adenomatous dPTCs resulted in a marked [53.8 +/- 7.9% (+/- SEM)] reduction in low calcium (Ca)-stimulated PTH secretion to levels equivalent to those in cell suppressed by high extracellular Ca (1.5 mM). Typically, these functional effects were optimal at antibody dilutions of 1:10(4) to 1:10(5). Cell viability was confirmed at the conclusion of each experiment by trypan blue exclusion (greater than 90-95%) and cell surface immunofluorescence. Parallel studies using the Ca-sensitive dye Quin-2 showed that inhibition of PTH secretion in 4F2-treated cells was associated with a concomitant increase in cytosolic Ca (Cai) of 188% in 0.5 mM Ca; these values also approached Cai levels in control cells incubated in high Ca. Mab controls, P3 X 63, which do not bind to dPTCs, and Mab LC7-2, which recognizes a different epitope of the same antigen as 4F2 on dPTCs, did not alter PTH secretion or Cai. Immunoprecipitation of 125I-labeled parathyroid cell extracts with MAb 4F2 demonstrated proteins with mol wt of approximately 145, 85, and 45 under nonreducing conditions and 85 and 45 kilodaltons after reduction with 5% mercaptoethanol. These studies suggest that 1) Mab-4F2 binding to its cell surface antigen inhibits PTH secretion by human adenomatous parathyroid cells in vitro; 2) the alterations in secretory function could be related to by an attendant increase in Cai; 3) the 4F2 antigen on dPTCs is a heterodimeric protein of (approximately) 85K and 45K; and 4) the 4F2 antigen may be an important component of the Ca-sensing and/or signal-transducing mechanism in this cell.

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Depolarizing response of rat parathyroid cells to divalent cations.

Cited by 88 publications

References 40 publications

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Novel regulatory aspects of the extracellular Ca2+-sensing receptor, CaR

Regulation of Parathyroid Hormone Secretion*

Binding of Monoclonal Antibody (4F2) to its Cell Surface Antigen on Dispersed Adenomatous Parathyroid Cells Raises Cytosolic Calcium and Inhibits Parathyroid Hormone Secretion*

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